Sulphonic acids, esterification

There are two chiral centres In (47) so a mixture of diastereoisomers is produced in 75 and 15% yields. Fortunately the major isomer is the analgesic. In fact only one enantiomer of this diastereo isomer is analgesic and so (48) is resolved with camphor sulphonic acid before esterification. The other enantiomer is a useful cough suppressant. 

Sulphonic acids are water soluble, viscous liquids. Their acidity is akin to that of sulphuric acid feey form salts with bases but fail to undergo esterification with alcohols. Their properties vary according to the nature of R some are prone to thermal decomposition. They are used as surfactants and in the dye industry some have biological uses. 2-Amino-ethanesulphonic acid is the only naturally occurring sulphonic acid. 

The diffusion of the large sucrose molecule may be so slow that a large proportion of the sulphonic acid groups inside the polymer become inaccessible and cannot participate in the reaction [506,508], as was also assumed for esterification (p. 361) and ester hydrolysis (p. 377). 

A recent procedure for the preparation of methyl esters involves refluxing the carboxylic acid with methanol and 2,2-dimethoxypropane in the presence of toluene-p-sulphonic acid as the catalyst (Expt 5.146). The water produced in the esterification process is effectively removed by acid-catalysed reaction with the ketal to give acetone and methanol. 

These sulphonate esters cannot be made by direct esterification of the sulphonic acids since further reaction of the ester with the alcohol gives rise to an ether by means of an alkyl-oxygen fission process. 

Sulphonic acids and their salts are analysed by GC after esterification with diazomethane or after chlorination with thionyl chloride or phosgene [119]. Reaction with thionyl chloride proceeds according to Scheme 5.14. A 0.5-g sample of sulphonic acid or its salt is placed into a round-bottomed flask fitted with a magnetic stirrer and a reflux condenser, 0.5 ml of dimethylformamide and 20 ml of thionyl chloride are added and the mixture is refluxed for several minutes up to 2 h (according to the character of the sample) until the evolution of gas from the reaction mixture ceases (detection with the aid of a bubbler filled with chlorobenzene). If a salt is chlorinated, solid chloride produced in the reaction mixture must be removed by dilution with dichloromethane and by careful filtration through a fine glass filter. Excess of thionyl chloride and solvent is evaporated carefully under decreased pressure. The residue is dissolved in a suitable solvent (CCU) and analysed by GC (silicone stationary phase, temperature 160°C). 

Fischer-Speier esterification to give a salt of an amino acid ester (by refluxing an alkanol with anhydrous HC1 or hot benzyl alcohol with toluene-/>-sulphonic acid) is straightforward. The fact that the nearby amino group is protonated when the carboxy group reacts to give a-amino acid esters does not slow the reaction down unduly a nearby positive site might have been expected to reduce the electrophilic character of the carboxy carbon atom. Without an acid catalyst, Walkylation can accompany esterification (Equation 4.6). 

Virtually all of the methods for determining acyl groups developed up to now are based on re-esterification of the initial compound with sulphuric acid, a mixture of methanol with hydrochloric or p-toluenesulphonic acid, or with a mixture of p-toluene-sulphonic acid and its methyl ester [165—170]. The esters formed in the reaction were determined by analysing an aliquot of the reaction solution or by blowing-off the reactor with a carrier gas. Alkaline hydrolysis with subsequent determination of acetic acid has also been used for identifying acyl groups [167]. 

Esterification of sulphonic acids with alcohols usually produces an equilibrium mixture. For example, reaction of trifluoromethanesulphonic acid with ethanol gives an equilibrium mixture of diethyl ether, the ester and the reactants383,384. Such an equilibrium may be driven to give the desired sulphonate ester by azeotropic removal of water385. 

As heterogeneous catalysts the ion- exchange resins containing sulphonic acid (-SO3H) groups are active in the esterification. The acids used as catalysts often undergo side reactions since they can in principle be esterified by the alcohols present in the system. 

Microwave-assisted esterification by a heterogeneous acid catalyst has been studied in a low dielectric constant medium (see Scheme 35) [64]. A continuous-flow setup has been devised in the system and the heterogeneous acid catalyst (Amberlyst A15 sulphonic acid cation-exchange resin) 61 localized in a polyethylene active flow cell. Use of a low dielectric constant medium (hexane) ensured absorption of microwave radiation only to the reacting species. In this case, the findings suggest a comparable esterification reaction under both microwave and thermal conditions. Furthermore, the presence of water in the catalytic resin resulted in a reduction of the reaction rate irrespective of the type... 

A process performance study has been conducted by David et al. [96] taking the coupling of the esterification reactions of 1-propanol and 2-propanol with propionic acid to pervaporation as a model system. Toluene sulphonic acid was applied as the homogeneous acid catalyst. A poly (vinyl alcohol)-based composite membrane, supplied by Carbone Lorraine-GFT, was used. Figure 5.10 shows the comparison between the esterification reaction with and without pervaporation. Without pervaporation, the conversion factor reaches a limit, which corresponds to the equilibrium of the esterification reaction. Coupling of the esterification to pervaporation allows the reaction to reach almost complete conversion. 

Possibly the simplest example of the first approach would be the substitution of a sulphonated polystyrene-divinylbenzene polymer ion-exchange resin (in free acid form) for p-toluene sulphonic acid as the catalyst in an esterification or other acid-catalysed chemical reaction (see section 11.7.2). The ion-exchange resin may be used in bead form and packed into a tubular reactor, or may be introduced as a powder and subsequently filtered off. Furthermore, the solid resin may prove less corrosive to the metal walls of an industrial reaction vessel. 

One of the early attempts of in situ activation was the reaction of carboxylic acids with sulphonic acid chlorides that was adopted for the homogeneous modification of cellulose. The exclusion of the base simplified the reaction medium and the isolation procedure [29]. There is an ongoing discussion about the mechanism which initiates esterification of cellulose with the carboxylic acids in the presence of p-toluenesulphonic acid chloride (TosCl). The mixed anhydride of p-toluenesulphonic acid (TosOH) and the carboxylic acid is favoured [30]. However, from H NMR experiments with acetic acid/TosCl, it was concluded that a mixture of acetic anhydride (2.21 ppm) and acetyl chloride (2.73 ppm) was responsible for the high reactivity of this system (Figs 16.2 and 16.3). 

Esterification.—Another way to improve the sometimes unsatisfactory N,N-dicyclohexylcarbodi-imide esterification method is to add catalytic quantities of toluene-p-sulphonic acid to the reaction mixture (c/. 3, 149). Esters can be obtained very rapidly and generally in high yields by reactions between 2-substituted 1,3-benzoxathiolium salts and alcohols (Scheme 30). One drawback could be the rather acidic conditions employed in the second step. A neat modification of the mixed-anhydride esterification method requires no added acid or base in the final step but uses an intramolecular cyclization as the driving... 

Methyl, ethyl, benzyl, benzhydryl, p-nitrobenzyl, p-methoxy-benzyl, 4-picolyl, j3j -trichloroethyl, j3-methylthioethyl, /J-p-toluenesulphonylethyl, and -p-nitrophenylthioethyl esters may be prepared directly from the acid and alcohol. TTie most usual method [4, 5] consists of heating the acid and an excess of the alcohol with an acid catalyst (e.g., Fischer-Speier, hydrochloric or sulphuric acid). The extent of reaction is improved if the water formed is removed by azeotropic distillation with an inert solvent (benzene, carbon tetrachloride, or chloroform). Considerable variation is possible in the natvire of the acid catalyst thus phosphoric acid [6], aryl sulphonic acids [7, 8, 9], alkyl sulphates [10], and acidic ion-exchange resins [11] may be employed. Removal of the water by azeotropic distillation during the formation of methyl esters is difficult and Brown and Lovette [12] introduced the novel reagent acetone dimethyl acetal (7) for the direct formation of methyl esters. In the presence of a trace of methanol and an acid catalyst the reagent acts as a scavenger of water formed by esterification and liberates further methanol for reaction. 

Cases are also known where a reaction product is firmly held to catalytic sites and diffuses out at a prohibitively low rate. The effect has been observed in several cases, including the esterification of alcohols, acting as reactant and solvent [16, 20]. It is thought that in these reactions water is the product which poisons the acidic sites of the sulphonic acid catalyst. A more straightforward case is the hydrolysis of amides where one of the reaction products, the amine, forms an ammonium salt with the resin acid and thus decreases the number of free acid groups [21]. Similarly, cationic reaction products (formed from cationic reactants) may be retained in the resin by virtue of its ion exchanger function. 

Maki-Arvela (1999) has developed a new polyolefin supported sulphonic acid catalyst for esterification of acetic acid with methanol. The esterification kinetics (pseudo-homogeneous) was modeled with a mechanistic rate equation, the parameters of which were determined by non-linear regression. The esterification rate constant of the most active modification of the new catalyst was 9.6 x 10 ° dm /(mol g min) at 328 K, which clearly exceeds the corresponding value obtained with a traditional (Amberlyst 15) polyvinyl benzene supported catalyst, 1.5 x 10 ° dm /(moP g min). 

Lee and Wilson (2014) emphasized SBA-15 with p6mm is notorious to transport bulk reaction media, whileKlT-6 with its interconnected/aJJ stracmre offers better in-pore accessibility of sulphonic acid sites. Results revealed PrS03H-KlT-6 produced higher turnover frequency (40 and 70%) compared to SBA-15 toward propanoic and hexanoic acid (Fig. 6.16). However, pore accessibility remains challenging for esterification of C16-C18 long chains. 

Figure 3. The esterification reaction of acetic acid with n-propanol is examined for /7-toluene-sulphonic acid and E-ePMO-SOsH. The conversions of n-propanol for both catalysts are presented in the graph.

Sulphonates.—Novel syntheses are reported for methyl arenesulphonates (activated benzene + Me03SF at 100 C) and more generally," employing R C0P(0)(0R 2 for esterification of sulphonic acids. A photo-Fries rearrangement (76) (77) is notable." ... 

When either of the reactants is sensitive to mineral acids, the esterification can often be successfully accomplished with the aid of a cation exchange resin (hydrogen form) in the presence of benzene. Zeo-Karb 225/H, a unifunctional sulphonated polystyrene resin in the hydrogen form, may be used. Thus good yields of isopropyl lactate may be obtained ... 

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